By definition, osteonecrosis means in situ death of bone cells, osteocytes, and hematopoietic and fatty marrow precursor cells, and it is most often thought to be due to bone marrow pressure (Kantor et al.1987
) or an occult subchondral fracture (Yamamoto and Bullough 2000
). Although the cells in the necrotic lesion die, the inorganic bone matrix is primarily unaffected and the bone will initially retain its load-bearing capacity (Parks and Engh 1997
). Regardless of cause, ingrowing blood vessels invade the necrotic bone from the surrounding living bone, and osteoclasts are brought into the lesion to resorb the necrotic bone matrix. A remodeling process starts, with simultaneous coupling of bone resorption and formation. The mechanical strength of the remodeling bone might be temporarily reduced, either due to the resorption of necrotic bone or to a fatigue stress fracture in necrotic bone that has not yet become revitalized. If the necrosis occurs in subchondral load-bearing bone, partial joint collapse and secondary osteoarthritis might be the final result (Tägil et al. 2004
, Lai et al. 2005
In the previous study of 40 patients at our hospital (Al-Rowaih et al. 1991
) with a similar but untreated series of knee osteonecrosis, patients with higher Lotke indices had worse outcome with a high frequency of joint surface collapse and subsequent surgery than those in the present, treated series. Only 10 of 40 patients had a good outcome in the original study with complete radiographical recovery, as compared to 10 of 17 in the present series (p = 0.03, Fisher’s exact test). 8 of 40 patients were considered intermediate due to development of osteoarthritis, but with minor symptoms compared to the present study where 4 of 17 of the bisphosphonate-treated patients developed mild osteoarthritis.
The incidence of secondary surgery appears to be less when bisphosphonates are given. In the original series, 22 of 40 patients were considered failures due to osteoarthritis and major symptoms. Of these patients, 13 underwent surgery with osteotomy, decompression, or prosthesis. In the present series, 2 of the 17 patents were failures because they needed surgery (p = 0.2, Fisher’s exact test). It is notable that none of these patients were able to complete the planned minimum 6 months of bisphosphonate treatment and they were the only patients not to do so. Although not operated, another patient in the bisphosphonate-treated group was considered a failure, as he developed severe osteoarthritis (Ahlbäck grade 3) and collapse of the joint surface. In the original series, the size of the lesion was found to be associated with an inferior outcome but in the present series no such association was found. In our series, lesions larger than the cutoff at Lotke index 30% healed without osteoarthritis, but lesions smaller in size also collapsed. In addition, time from the start of symptoms to start of treatment appeared to be unrelated to outcome.
In the only randomized trial using bisphosphonates in osteonecrosis (of the hip) (Lai et al. 2005
), a fixed treatment time of 6 months was set. In our study, treatment was continued until the central region started to increase in radiographic density, indicating osteoblast activity in the center and a hypothetically regained mechanical strength. It is not known how long treatment should last.
In conclusion, the outcome for our patients in the present series appears to have been better than in the previous, untreated series (al Rowai 1991
), and calls for a prospective randomized study to determine whether bisphosphonates are capable of changing the outcome. Perhaps a prolonged period of partial weight bearing would be as effective, or maybe both are needed. In the future, other drugs might also be used—such as RANK-ligand antibodies—which besides being more short-acting, have been shown to be more effective than bisphosphonates in experimentally induced osteonecrosis (Kim et al. 2006